This project is designed to prepare a GMP quality investigational HIV vaccine and complete the preclinical and laboratory studies needed for clinical studies of a multicomponent HIV-1 adenoviral vector vaccine. The hypothesis is that the vaccine will be safe for human administration and elicit immune responses to HIV-1. Subjects receive adenovector vaccine either as a single agent or as a boost after priming with plasmid DNA vaccines. The Vaccine Research Center (VRC), NIAID is developing a novel prime-boost HIV vaccine strategy directed at the most globally prevalent HIV subtypes (clades). VRC's HIV prime-boost candidate is designed to elicit immune responses to HIV sequences from stains most commonlyHIV infections around the world. The VRC is developing modified adenovectors that should be less susceptible to the potential inhibition effects of high prevalance of Ad5 neutralising antibodies.